Antibiotic resistance of bacteria agents (Staphylococcis aureus, Pseudomonas aeruginosa, Escherichia coli and Streptococcus pyogenes) of nosocomial wound infections, were assessed by in vitro susceptibility testing, evaluating the possible drug interactions among several antibiotics and the plasmid profile of DNA of isolate. Ninety-six clinical isolates of (S.aureus, P aeruginosa, E coll and S pyogenes) obtained from two different Hospitals, were collected. Suceptibility test with 17 antibiotics were performed by the Kirby-Bauer disk diffusion method and Minimal Inhibitory Concentrations [MICs] were determined by macrobroth dilution methodology. There is significant difference in the resistance between Staphylococcus aureus isolates (43(100%) and Pseudomonas aeruginosa isolates (32(91.4%), [P<0.05]. Resistance to ofloxacin, erythromycin, norfloxacin, tetracyclines and chloramphenicol were more common. Highly resistant isolates were selected for the drug combination. Staphylococcus aureus (C.I) and Pseudomonas aeruginosa (C.I) were used as control isolates. Erythromycin had a high MIC50 value against the E coli isolates while it had a moderate effect 47% on all the 1solates. Combination of ciprofloxacin and erythromycin was fully synergistic against one S. pyogenes isolate, while the same combination resulted in indifferent effect in most of the isolates. Combination therapy could be used to prevent the development of resistance and to enhanced antibacterial efficacy. Plasmid bands were seen in all the resistant isolates as revealed through agarose gel electrophoresis. The susceptibility test performed in this study suggests that nosocomial wound infections were caused by organisms that are highly resistance to antibiotics. It is imperative that hygienic conditions and surveillance initiative be focused in Hospitals in Nigeria to monitor and limit antimicrobial resistance and the spread of these nosocomial organisms, that is a major risk to human health because of its impact on morbidity, mortality and health care costs.

Omenyi A.S, Okpala C.I, Umeh C.L, Anazodo C.A, Chidozie C.P, Oghonim P.AN, Abana, C.C, Ogbunude, A. P, Ebo P.U, Ojeah, I.K, "Antibiotic Resistance in Nigerian Hospitals: Phenotypic Evidence, Genetic Drivers, and Control Implications in Antimicrobial Stewardship" International Journal of Advance Research in Science, Management, Engineering and Technology, V1(3): Page(01-26) July - August 2026. ISSN: 3139-1141. www.ijarsmet.com. Published by Scientific and Academic Research Publishing.